Hepatitis C and hepatic steatosis

QJM: An International Journal of Medicine

Volumn 103, Issue 5, 2010, Pages 293-303

  Patel, J H ^a   Cobbold, J F L ^a   Thomas, H C ^a   Taylor Robinson, S D ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; ALPHA TOCOPHEROL; ASCORBIC ACID; FLUINDOSTATIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ICOSAPENTAENOIC ACID; INTERFERON; LOW DENSITY LIPOPROTEIN; METFORMIN; MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN; PEGINTERFERON; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PLACEBO; RIBAVIRIN; ROSIGLITAZONE; STEROL REGULATORY ELEMENT BINDING PROTEIN; VERY LOW DENSITY LIPOPROTEIN;

ANTIVIRAL THERAPY; CHOLESTEROL SYNTHESIS; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DISEASE ASSOCIATION; DISEASE COURSE; FATTY LIVER; HEPATITIS C; HUMAN; INSULIN RESISTANCE; LIPID METABOLISM; LIVER FIBROSIS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; TREATMENT RESPONSE; VIRUS LOAD; VIRUS REPLICATION; VIRUS TYPING;

EID: 77953055091     PISSN: 14602725     EISSN: 14602393     Source Type: Journal    
DOI: 10.1093/qjmed/hcp192     Document Type: Review

References (103)

1. World Health Organisation. Hepatitis C - Global Surveillance Update. Weekly Epidemiological Record 2000; 75:17-28.
2. Esteban JI, Sauleda S, Quer J. The changing epidemiology of hepatitis C virus infection in Europe. J Hepatol 2008; 48:148-62.
3. Frank C, Mohamed MK, Strickland GT, Lavanchy D, Arthur RR, Magder LS, et al. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet 2000; 355:887-91.
4. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002; 346:1221-31.
5. Clark JM, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology 2002; 122:1649-57.
6. Perz J, Farrington L, Pecoroco C, Hutin Y, Armstrong G. Estimated Global Prevalence of Hepatitis C. In: Proceedings of the 42nd Annual Meeting of Infectious Diseases of America, Sept 30-Oct 3, 2004. Boston, MA, USA.
7. Hwang SJ, Luo JC, Chu CW, Lai CR, Lu CL, Tsay SH, et al. Hepatic steatosis in chronic hepatitis C virus infection: prevalence and clinical correlation. J Gastroenterol Hepatol 2001; 16:190-5.
8. Thomopoulos KC, Arvaniti V, Tsamantas AC, Dimitropoulou D, Gogos CA, Siagris D, et al. Prevalence of liver steatosis in patients with chronic hepatitis B: a study of associated factors and of relationship with fibrosis. Eur J Gastroenterol Hepatol 2006; 18:233-7.
9. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005; 365:1415-28.
10. Sheikh MY, Choi J, Qadri I, Friedman JE, Sanyal AJ. Hepatitis C virus infection: molecular pathways to metabolic syndrome. Hepatology 2008; 47:2127-33.
11. Korenaga M, Wang T, Li Y, Showalter LA, Chan T, Sun J, et al. Hepatitis C virus core protein inhibits mitochondrial electron transport and increases reactive oxygen species (ROS) production. J Biol Chem 2005; 280:37481-8.
12. Okuda M, Li K, Beard MR, Showalter LA, Scholle F, Lemon SM, et al. Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology 2002; 122:366-75.
13. Moriya K, Nakagawa K, Santa T, Shintani Y, Fujie H, Miyoshi H, et al. Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocarcinogenesis. Cancer Res 2001; 61:4365-70.
14. Perlemuter G, Sabile A, Letteron P, Vona G, Topilco A, Chretien Y, et al. Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion: a model of viral-related steatosis. FASEB J 2002; 16:185-94.
15. Miyanari Y, Atsuzawa K, Usuda N, Watashi K, Hishiki T, Zayas M, et al. The lipid droplet is an important organelle for hepatitis C virus production. Nat Cell Biol 2007; 9:1089-97.
16. Lyn RK, Kennedy DC, Sagan SM, Blais DR, Rouleau Y, Pegoraro AF, et al. Direct imaging of the disruption of hepatitis C virus replication complexes by inhibitors of lipid metabolism. Virology 2009; 394:130-42.
17. Ye J. Reliance of host cholesterol metabolic pathways for the life cycle of hepatitis C virus. PLoS Pathog 2007; 3:e108.
18. Ye J, Wang C, Sumpter R Jr, Brown MS, Goldstein JL, Gale M Jr. Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation. Proc Natl Acad Sci USA 2003; 100:15865-70.
19. Wang C, Gale M Jr, Keller BC, Huang H, Brown MS, Goldstein JL, et al. Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication. Mol Cell 2005; 18:425-34.
20. Kapadia SB, Chisari FV. Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids. Proc Natl Acad Sci USA 2005; 102:2561-6.
21. Leu GZ, Lin TY, Hsu JT. Anti-HCV activities of selective polyunsaturated fatty acids. Biochem Biophys Res Commun 2004; 318:275-80.
22. Domitrovich AM, Felmlee DJ, Siddiqui A. Hepatitis C virus nonstructural proteins inhibit apolipoprotein B100 secretion. J Biol Chem 2005; 280:39802-8.
23. Petit JM, Benichou M, Duvillard L, Jooste V, Bour JB, Minello A, et al. Hepatitis C virus-associated hypobetalipoproteinemia is correlated with plasma viral load, steatosis, and liver fibrosis. Am J Gastroenterol 2003; 98:1150-4.
24. Serfaty L, Andreani T, Giral P, Carbonell N, Chazouilleres O, Poupon R. Hepatitis C virus induced hypobetalipoproteinemia: a possible mechanism for steatosis in chronic hepatitis C. J Hepatol 2001; 34:428-34.
25. Mirandola S, Realdon S, Iqbal J, Gerotto M, Dal Pero F, Bortoletto G, et al. Liver microsomal triglyceride transfer protein is involved in hepatitis C liver steatosis. Gastroenterology 2006; 130:1661-9.
26. Dai CY, Chuang WL, Ho CK, Hsieh MY, Huang JF, Lee LP, et al. Associations between hepatitis C viremia and low serum triglyceride and cholesterol levels: a community-based study. J Hepatol 2008; 49:9-16.
27. Jarmay K, Karacsony G, Nagy A, Schaff Z. Changes in lipid metabolism in chronic hepatitis C. World J Gastroenterol 2005; 11:6422-8.
28. Siagris D, Christofidou M, Theocharis GJ, Pagoni N, Papadimitriou C, Lekkou A, et al. Serum lipid pattern in chronic hepatitis C: histological and virological correlations. J Viral Hepat 2006; 13:56-61.
29. Ferre P. The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity. Diabetes 2004; 53(Suppl. 1):S43-50.
30. Dharancy S, Malapel M, Perlemuter G, Roskams T, Cheng Y, Dubuquoy L, et al. Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection. Gastroenterology 2005; 128:334-42.
31. de Gottardi A, Pazienza V, Pugnale P, Bruttin F, Rubbia-Brandt L, Juge-Aubry CE, et al. Peroxisome proliferator-activated receptor-alpha and -gamma mRNA levels are reduced in chronic hepatitis C with steatosis and genotype 3 infection. Aliment Pharmacol Ther 2006; 23:107-14.
32. Eberle D, Hegarty B, Bossard P, Ferre P, Foufelle F. SREBP transcription factors: master regulators of lipid homeostasis. Biochimie 2004; 86:839-48.
33. Waris G, Felmlee DJ, Negro F, Siddiqui A. Hepatitis C virus induces proteolytic cleavage of sterol regulatory element binding proteins and stimulates their phosphorylation via oxidative stress. J Virol 2007; 81:8122-30.
34. Kim KH, Hong SP, Kim K, Park MJ, Kim KJ, Cheong J. HCV core protein induces hepatic lipid accumulation by activating SREBP1 and PPARgamma. Biochem Biophys Res Commun 2007; 355:883-8.
35. Oem JK, Jackel-Cram C, Li YP, Zhou Y, Zhong J, Shimano H, et al. Activation of sterol regulatory element-binding protein 1c and fatty acid synthase transcription by hepatitis C virus non-structural protein 2. J Gen Virol 2008; 89(Pt 5):1225-30.
36. Rubbia-Brandt L, Quadri R, Abid K, Giostra E, Male PJ, Mentha G, et al. Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3. J Hepatol 2000; 33:106-15.
37. Kumar D, Farrell GC, Fung C, George J. Hepatitis C virus genotype 3 is cytopathic to hepatocytes: Reversal of hepatic steatosis after sustained therapeutic response. Hepatology 2002; 36:1266-72.
38. Poynard T, Ratziu V, McHutchison J, Manns M, Goodman Z, Zeuzem S, et al. Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C. Hepatology 2003; 38:75-85.
39. Mehta SH, Brancati FL, Strathdee SA, Pankow JS, Netski D, Coresh J, et al. Hepatitis C virus infection and incident type 2 diabetes. Hepatology 2003; 38:50-6.
40. Hui JM, Sud A, Farrell GC, Bandara P, Byth K, Kench JG, et al. Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression [corrected]. Gastroenterology 2003; 125:1695-704.
41. Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Tsukamoto K, Kimura S, et al. Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology 2004; 126:840-8.
42. Hotamisligil GS, Johnson RS, Distel RJ, Ellis R, Papaioannou VE, Spiegelman BM, et al. Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science 1996; 274:1377-9.
43. Hofmann C, Lorenz K, Braithwaite SS, Colca JR, Palazuk BJ, Hotamisligil GS, et al. Altered gene expression for tumor necrosis factor-alpha and its receptors during drug and dietary modulation of insulin resistance. Endocrinology 1994; 134:264-70.
44. Hotamisligil GS, Budavari A, Murray D, Spiegelman BM. Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. Central role of tumor necrosis factor-alpha. J Clin Invest 1994; 94:1543-9.
45. Kanety H, Feinstein R, Papa MZ, Hemi R, Karasik A. Tumor necrosis factor alpha-induced phosphorylation of insulin receptor substrate-1 (IRS-1). Possible mechanism for suppression of insulin-stimulated tyrosine phosphorylation of IRS-1. J Biol Chem 1995; 270:23780-4.
46. Liu LS, Spelleken M, Rohrig K, Hauner H, Eckel J. Tumor necrosis factor-alpha acutely inhibits insulin signaling in human adipocytes: implication of the p80 tumor necrosis factor receptor. Diabetes 1998; 47:515-22.
47. Valverde AM, Teruel T, Navarro P, Benito M, Lorenzo M. Tumor necrosis factor-alpha causes insulin receptor substrate-2-mediated insulin resistance and inhibits insulin-induced adipogenesis in fetal brown adipocytes. Endocrinology 1998; 139:1229-38.
48. Fernandez-Veledo S, Hernandez R, Teruel T, Mas JA, Ros M, Lorenzo M. Ceramide mediates TNF-alpha-induced insulin resistance on GLUT4 gene expression in brown adipocytes. Arch Physiol Biochem 2006; 112:13-22.
49. Negro F. Hepatitis C virus and liver steatosis: is it the virus? Yes it is, but not always. Hepatology 2002; 36:1050-2.
50. Camma C, Bruno S, Di Marco V, Di Bona D, Rumi M, Vinci M, et al. Insulin resistance is associated with steatosis in nondiabetic patients with genotype 1 chronic hepatitis C. Hepatology 2006; 43:64-71.
51. Fartoux L, Poujol-Robert A, Guechot J, Wendum D, Poupon R, Serfaty L. Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C. Gut 2005; 54:1003-8.
52. Capeau J. Insulin resistance and steatosis in humans. Diabetes Metab 2008; 34(6 Pt 2):649-57.
53. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005; 115:1343-51.
54. Cornier MA, Dabelea D, Hernandez TL, Lindstrom RC, Steig AJ, Stob NR, et al. The metabolic syndrome. Endocr Rev 2008; 29:777-822.
55. Taskinen MR. Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia 2003; 46:733-49.
56. Roden M. Mechanisms of Disease: hepatic steatosis in type 2 diabetes-pathogenesis and clinical relevance. Nat Clin Pract Endocrinol Metab 2006; 2:335-48.
57. Poli G. Pathogenesis of liver fibrosis: role of oxidative stress. Mol Aspects Med 2000; 21:49-98.
58. Otani K, Korenaga M, Beard MR, Li K, Qian T, Showalter LA, et al. Hepatitis C virus core protein, cytochrome P450 2E1, and alcohol produce combined mitochondrial injury and cytotoxicity in hepatoma cells. Gastroenterology 2005; 128:96-107.
59. Ando M, Korenaga M, Hino K, Ikeda M, Kato N, Nishina S, et al. Mitochondrial electron transport inhibition in full genomic hepatitis C virus replicon cells is restored by reducing viral replication. Liver Int 2008; 28:1158-66.
60. Koike K. Steatosis in chronic hepatitis C: fuel for over-production of oxidative stress? J Gastroenterol 2005; 40:664-5.
61. Kitase A, Hino K, Furutani T, Okuda M, Gondo T, Hidaka I, et al. In situ detection of oxidized n-3 polyunsaturated fatty acids in chronic hepatitis C: correlation with hepatic steatosis. J Gastroenterol 2005; 40:617-24.
62. Paradis V, Mathurin P, Kollinger M, Imbert-Bismut F, Charlotte F, Piton A, et al. In situ detection of lipid peroxidation in chronic hepatitis C: correlation with pathological features. J Clin Pathol 1997; 50:401-6.
63. Leandro G, Mangia A, Hui J, Fabris P, Rubbia-Brandt L, Colloredo G, et al. Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data. Gastroenterology 2006; 130:1636-42.
64. Adinolfi LE, Gambardella M, Andreana A, Tripodi MF, Utili R, Ruggiero G. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology 2001; 33:1358-64.
65. Monto A, Alonzo J, Watson JJ, Grunfeld C, Wright TL. Steatosis in chronic hepatitis C: relative contributions of obesity, diabetes mellitus, and alcohol. Hepatology 2002; 36:729-36.
66. Hourigan LF, Macdonald GA, Purdie D, Whitehall VH, Shorthouse C, Clouston A, et al. Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis. Hepatology 1999; 29:1215-9.
67. Fartoux L, Chazouilleres O, Wendum D, Poupon R, Serfaty L. Impact of steatosis on progression of fibrosis in patients with mild hepatitis C. Hepatology 2005; 41:82-7.
68. Westin J, Nordlinder H, Lagging M, Norkrans G, Wejstal R. Steatosis accelerates fibrosis development over time in hepatitis C virus genotype 3 infected patients. J Hepatol 2002; 37:837-42.
69. Castera L, Hezode C, Roudot-Thoraval F, Bastie A, Zafrani ES, Pawlotsky JM, et al. Worsening of steatosis is an independent factor of fibrosis progression in untreated patients with chronic hepatitis C and paired liver biopsies. Gut 2003; 52:288-92.
70. Rubbia-Brandt L, Fabris P, Paganin S, Leandro G, Male PJ, Giostra E, et al. Steatosis affects chronic hepatitis C progression in a genotype specific way. Gut 2004; 53: 406-12.
71. Patton HM, Patel K, Behling C, Bylund D, Blatt LM, Vallee M, et al. The impact of steatosis on disease progression and early and sustained treatment response in chronic hepatitis C patients. J Hepatol 2004; 40:484-90.
72. Paradis V, Dargere D, Vidaud M, De Gouville AC, Huet S, Martinez V, et al. Expression of connective tissue growth factor in experimental rat and human liver fibrosis. Hepatology 1999; 30:968-76.
73. Williams EJ, Gaca MD, Brigstock DR, Arthur MJ, Benyon RC. Increased expression of connective tissue growth factor in fibrotic human liver and in activated hepatic stellate cells. J Hepatol 2000; 32:754-61.
74. Abou-Shady M, Friess H, Zimmermann A, di Mola FF, Guo XZ, Baer HU, et al. Connective tissue growth factor in human liver cirrhosis. Liver 2000; 20:296-304.
75. Paradis V, Perlemuter G, Bonvoust F, Dargere D, Parfait B, Vidaud M, et al. High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. Hepatology 2001; 34(4 Pt 1):738-44.
76. Gressner AM, Yagmur E, Lahme B, Gressner O, Stanzel S. Connective tissue growth factor in serum as a new candidate test for assessment of hepatic fibrosis. Clin Chem 2006; 52:1815-7.
77. Hora C, Negro F, Leandro G, Oneta CM, Rubbia-Brandt L, Muellhaupt B, et al. Connective tissue growth factor, steatosis and fibrosis in patients with chronic hepatitis C. Liver Int 2008; 28:370-6.
78. Cobbold JF, Patel JH, Goldin RD, North BV, Crossey MM, Fitzpatrick J, et al. Hepatic lipid profiling in chronic hepatitis C: an in vitro and in vivo proton magnetic resonance spectroscopy study. J Hepatol 2009; 52:16-24.
79. Svegliati Baroni G, D'Ambrosio L, Ferretti G, Casini A, Di Sario A, Salzano R, et al. Fibrogenic effect of oxidative stress on rat hepatic stellate cells. Hepatology 1998; 27:720-6.
80. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001; 358:958-65.
81. Akuta N, Suzuki F, Tsubota A, Suzuki Y, Someya T, Kobayashi M, et al. Efficacy of interferon monotherapy to 394 consecutive naive cases infected with hepatitis C virus genotype 2a in Japan: therapy efficacy as consequence of tripartite interaction of viral, host and interferon treatment-related factors. J Hepatol 2002; 37:831-6.
82. Harrison SA, Brunt EM, Qazi RA, Oliver DA, Neuschwander-Tetri BA, Di Bisceglie AM, et al. Effect of significant histologic steatosis or steatohepatitis on response to antiviral therapy in patients with chronic hepatitis C. Clin Gastroenterol Hepatol 2005; 3:604-9.
83. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 347:975-82.
84. Chu CJ, Lee SD, Hung TH, Lin HC, Hwang SJ, Lee FY, et al. Insulin resistance is a major determinant of sustained virological response in genotype 1 chronic hepatitis C patients receiving peginterferon alpha-2b plus ribavirin. Aliment Pharmacol Ther 2009; 29:46-54.
85. Romero-Gomez M, Fernandez-Rodriguez CM, Andrade RJ, Diago M, Alonso S, Planas R, et al. Effect of sustained virological response to treatment on the incidence of abnormal glucose values in chronic hepatitis C. J Hepatol 2008; 48:721-7.
86. Conjeevaram HS, Kleiner DE, Everhart JE, Hoofnagle JH, Zacks S, Afdhal NH, et al. Race, insulin resistance and hepatic steatosis in chronic hepatitis C. Hepatology 2007; 45:80-7.
87. Dai CY, Huang JF, Hsieh MY, Hou NJ, Lin ZY, Chen SC, et al. Insulin resistance predicts response to peginterferon-alpha/ribavirin combination therapy in chronic hepatitis C patients. J Hepatol 2009; 50:712-8.
88. Poustchi H, Negro F, Hui J, Cua IH, Brandt LR, Kench JG, et al. Insulin resistance and response to therapy in patients infected with chronic hepatitis C virus genotypes 2 and 3. J Hepatol 2008; 48:28-34.
89. Hickman IJ, Clouston AD, Macdonald GA, Purdie DM, Prins JB, Ash S, et al. Effect of weight reduction on liver histology and biochemistry in patients with chronic hepatitis C. Gut 2002; 51:89-94.
90. Ikeda M, Abe K, Yamada M, Dansako H, Naka K, Kato N. Different anti-HCV profiles of statins and their potential for combination therapy with interferon. Hepatology 2006; 44:117-25.
91. Bader T, Fazili J, Madhoun M, Aston C, Hughes D, Rizvi S, et al. Fluvastatin inhibits hepatitis C replication in humans. Am J Gastroenterol 2008; 103:1383-9.
92. Singh V, Carey EJ, Rudraraju M, Rosati MJ, Grumeretz CA, Balan V, et al. Role of HMG-CoA reductase therapy in hepatitis c (HCV) treatment outcomes. Gastroenterology 2007; 132:A789-90.
93. Tomioka K, Kakibuchi N, Murakami Y, Kawakami T, Takaguchi K, Kita K, et al. Effects of eicosapentaenoic acid supplementation in the treatment of chronic hepatitis C patients. J Nutrit Sci Vitaminol 2005; 51:419-25.
94. Tiikkainen M, Hakkinen AM, Korsheninnikova E, Nyman T, Makimattila S, Yki-Jarvinen H. Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes 2004; 53:2169-76.
95. Bajaj M, Suraamornkul S, Pratipanawatr T, Hardies LJ, Pratipanawatr W, Glass L, et al. Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes. Diabetes 2003; 52:1364-70.
96. Mayerson AB, Hundal RS, Dufour S, Lebon V, Befroy D, Cline GW, et al. The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes. Diabetes 2002; 51:797-802.
97. Romero-Gomez M, Diago M, Andrade RJ, Calleja JL, Salmeron J, Fernandez-Rodriguez CM, et al. Metformin with peginterferon alfa-2a and ribavirin in the treatment of naive genotype 1 chronic hepatitis C patients with insulin resistance (Tric-1): final results of a randomized and double-blinded trial. Hepatology 2008; 48:380A-380A.
98. Adler M, Matloff JL, Boxer AS, Han HS, Vachon ML, Carriero DC, et al. In chronic hepatitis C (Hcv), pretreatment with thiazolidinediones (Tzds) or metformin decreases insulin resistance (Ir) and Hcv viral load and increases early virologic response (Evr). Hepatology 2008; 48:1156A-1156A.
99. Merat S, Jabbari H, Sharifi AH, Zaer-Rezaee H, Fakbarzadeh E, Asadi R, et al. The effect of adding metformin to the treatment of hepatitis C: a preliminary report of a randomized controlled trial. J Hepatol 2008; 48:S304-S304.
100. Penin F, Dubuisson J, Rey FA, Moradpour D, Pawlotsky JM. Structural biology of hepatitis C virus. Hepatology 2004; 39:5-19.
101. Price DA, Bassendine MF, Norris SM, Golding C, Toms GL, Schmid ML, et al. Apolipoprotein epsilon3 allele is associated with persistent hepatitis C virus infection. Gut 2006; 55:715-8.
102. Monazahian M, Bohme I, Bonk S, Koch A, Scholz C, Grethe S, et al. Low density lipoprotein receptor as a candidate receptor for hepatitis C virus. J Med Virol 1999; 57:223-9.
103. Ehnholm C, Aho K, Huttunen JK, Kostiainen E, Mattila K, Pakkarainen J, et al. Effect of interferon on plasma lipoproteins and on the activity of postheparin plasma lipases. Arteriosclerosis 1982; 2:68-73.